Why Does it Take So Long for the FDA to Approve New Drugs?

By Ronald L. Scott

Laboratory and animal studies have recently indicated that new highly effective drugs for the treatment of cancer may soon be available. Some patients are already demanding the new drugs and cannot understand why are they are not yet available. Before the Food and Drug Administration (FDA) will approve a new drug, the manufacturer must prove that the drug is both safe and effective.

The research and approval process is complicated, time-consuming and costly. The FDA estimates that, on average, it takes eight and half years to study and test a new drug before it receives FDA approval, including laboratory and animal testing, as well as clinical trials using human subjects. The FDA first becomes involved in drug research after a pharmaceutical company has largely completed laboratory and animal testing. During the early stages of research, the drug "sponsor" (usually a pharmaceutical company) analyzes the drug’s physical and chemical properties in the laboratory, and studies its pharmacologic and toxic effects in laboratory animals. If results of such testing are promising, clinical trials using human subjects are conducted in three phases. The FDA chart below shows the usual time frames and purposes of each of the phases.

Testing in Humans
 
Number of Patients
Length
Purpose
Percent of Drugs Successfully Tested*
Phase 1
20-100
Several months
Mainly safety
70 percent
Phase 2
Up to several hundred
Several months to 2 years
Some short-term safety but mainly effectiveness
33 percent
Phase 3
Several hundred to several thousand
1-4 years
Safety, dosage, effectiveness
25-30 percent

 * For example, of 100 drugs for which investigational new drug applications are submitted to FDA, about 70 will successfully complete phase 1 trials and go on to phase 2; about 33 of the original 100 will complete phase 2 and go to phase 3; and 25 to 30 of the original 100 will clear phase 3 (and, on average, about 20 of the original 100 will ultimately be approved for marketing).
Patients seeking early access to an investigational drug may seek to volunteer to participate in clinical trials of the drug. However, it is sometimes difficult to assess the efficacy of a new drug where measurements of disease or effect may be subjective, i.e., essentially a matter of interpretation by the patient or physician. Most clinical trials use a control group to help reduce or eliminate such subjectivity. The control group in such a clinical trial receives a placebo rather than the investigational drug. Patients are randomly chosen for each group. Studies may be single-blind, where the patients do not know whether they are receiving a placebo or investigational drug, or double-blind, where even the investigators do not know which patients are assigned to each group. Science recognizes that bias can operate like a self-fulfilling prophecy, and use of randomized double-blind studies removes both patient and investigator bias. However, patients in such studies for the purpose of obtaining early access to an investigational drug run the risk of being assigned to the control group.

The FDA has been criticized for its lengthy approval process and for denying patients not participating in clinical trials access to promising investigational drugs. The FDA has long allowed the emergency use of unapproved, investigational drugs to help desperately ill and dying patients under the general rubric of "compassionate use." Also, beginning in 1987, the FDA changed its regulations to specifically authorize use of investigational new drugs (INDs) for treatment, so-called Treatment INDs. Treatment INDs can allow promising investigational drugs to be available as early as possible for patients with serious or life-threatening diseases, but ensure that controlled trials proceed to demonstrate the drug’s safety and efficacy.

05/08/98